Electron microscopic observations of surface projections on Chlamydia psittaci reticulate bodies.
Electron microscopic observations were carried out to confirm the presence of surface projections on Chlamydia psittaci reticulate bodies (RBs). The morphology of the projections on RBs was identical with that on elementary bodies (EBs); one end of each projection was connected with the cytoplasmic membrane, but the other end of the projection protruded beyond the cell wall through a fine hole or rosette in the cell wall. The results demonstrated that the rosettes seen in RB cell walls were morphological markers indicating the presence of the surface projections. A statistical anaylsis of the number of projections on EBs and the number of rosettes in RB cell walls prepared at 10, 15, and 20 h after infection demonstrated that all RBs had the projections and that the number of projections was maximal by 10 h after infection and then decreased gradually to approximately the same number of projections on EBs.


Controlling Enzymatic Polymerization from Surfaces with Switchable Bioaffinity.
The affinity of surfaces toward proteins is found to be a key parameter to govern the synthesis of polymer brushes by surface-initiated biocatalytic atom transfer radical polymerization (SI-bioATRP). While the "ATRPase" hemoglobin (Hb) stimulates only a relatively slow growth of protein repellent brushes, the synthesis of thermoresponsive grafts can be regulated by switching the polymer's attraction toward proteins across its lower critical solution temperature (LCST). Poly(N-isopropylacrylamide) (PNIPAM) brushes are synthesized in discrete steps of thickness at temperatures above LCST, while the biocatalyst layer is refreshed at T < LCST. Multistep surface-initiated biocatalytic ATRP demonstrates a high degree of control, results in high chain end group fidelity and enables the synthesis of multiblock copolymer brushes under fully aqueous conditions. The activity of Hb can be further modulated by tuning the accessibility of the heme pocket within the protein. Hence, the multistep polymerization is accelerated at acid pH, where the enzyme undergoes a transition from its native to a molten globule conformation. The controlled synthesis of polymer brushes by multistep SI-bioATRP highlights how a biocatalytic synthesis of grafted polymer films can be precisely controlled through the modulation of the polymer's interfacial physicochemical properties, in particular of the affinity of the surface toward proteins. This is not only of importance to gain a predictive understanding of surface-confined enzymatic polymerizations, but also represents a new way to translate bioadhesion into a controlled functionalization of materials.


Evaluation of Module Dynamics in Functional Brain Networks After Stroke.
The brain's functional network can be analyzed as a set of distributed functional modules. Previous studies using the static method suggested the modularity of the brain function network decreased due to stroke; however, how the modular network changes after stroke, particularly over time, is far from understood. This study collected resting-state functional MRI data from 15 stroke patients and 15 age-matched healthy controls. The patients exhibit distinct clinical symptoms, presenting in mild (n = 6) and severe (n = 9) subgroups. By using a multilayer network model, a dynamic modular structure was detected and corresponding interaction measurements were calculated. The results demonstrated that the module structure and interaction had changed following the stroke. Importantly, the significant differences in dynamic interaction measures demonstrated that the module interaction alterations were not independent of the initial degree of clinical severity. Mild patients were observed to have a significantly lower between-module interaction than severe patients as well as healthy controls. In contrast, severe patients showed remarkably lower within-module interaction and had a reduced overall interaction compared to healthy controls. These findings contributed to the development of post-stroke dynamics analysis and shed new light on brain network interaction for stroke patients.Clinical relevance- Dynamic module interaction analysis underpins the post-stroke functional plasticity and reorganization, and may enable new insight into rehabilitation strategies to promote recovery of function.


Modelling apical columnar epithelium mechanics from circumferential contractile fibres.
Simple columnar epithelia are formed by individual epithelial cells connecting together to form single cell high sheets. They are a main component of many important body tissues and are heavily involved in both normal and cancerous cell activities. Prior experimental observations have identified a series of contractile fibres around the circumference of a cross section located in the upper (apical) region of each cell. While other potential mechanisms have been identified in both the experimental and theoretical literature, these circumferential fibres are considered to be the most likely mechanism controlling movement of this cross section. Here, we investigated the impact of circumferential contractile fibres on movement of the cross section by creating an alternate model where movement is driven from circumferential contractile fibres, without any other potential mechanisms. In this model, we utilised a circumferential contractile fibre representation based on investigations into the movement of contractile fibres as an individual system, treated circumferential fibres as a series of units, and matched our model simulation to experimental geometries. By testing against laser ablation datasets sourced from existing literature, we found that circumferential fibres can reproduce the majority of cross-sectional movements. We also investigated model predictions related to various aspects of cross-sectional movement, providing insights into epithelium mechanics and demonstrating the usefulness of our modelling approach.


A Reversible Fluorescent Probe for Real-Time Quantitative Monitoring of Cellular Glutathione.
The ability to monitor and quantify glutathione (GSH) in live cells is essential in order to gain a detailed understanding of GSH-related pathological events. However, owing to their irreversible response mechanisms, most existing fluorescent GSH probes are not suitable for this purpose. We have developed a ratiometric fluorescent probe (QG-1) for quantitatively monitoring cellular GSH. The probe responds specifically and reversibility to GSH with an ideal dissociation constant (Kd ) of 2.59 mm and a fast response time (t1/2 =5.82 s). We also demonstrate that QG-1 detection of GSH is feasible in a model protein system. QG-1 was found to have extremely low cytotoxicity and was applied to determine the GSH concentration in live HeLa cells (5.40±0.87 mm).


Mobility of chloroaromatic compounds in soil: case studies of Swedish chlorophenol-contaminated sawmill sites.
This paper summarizes recent studies on the environmental fate of chloroaromatic compounds in chlorophenol (CP)-contaminated soil and groundwater at Swedish sawmill sites. Relative proportions of CPs, polychlorinated phenoxy phenols (PCPPs), polychlorinated diphenyl ethers (PCDEs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) were determined in preservatives, particulate organic matter (POM), dissolved organic matter (DOM), groundwater, and particles filtered from groundwater. All compound classes were found in the different compartments. The fraction of PCPPs, PCDEs, PCDDs, and PCDFs had increased in the soil samples relative to the proportions in the preservatives. This increase showed correlation with the hydrophobicity, that is, PCDDs had the largest increase. Similar correlation was found between hydrophobicity and the importance of partitioning to POM over DOM. The more water soluble compound group, CP, was found equally distributed between POM and DOM. For PCPPs, PCDEs, PCDDs, and PCDFs, the relative partitioning to POM increased with increased hydrophobicity. Despite the relative partitioning towards POM, compared with DOM, cotransport with DOM and suspended colloidal fractions was found to substantially increase the transport of these compounds in the groundwater samples.


Danazol: objective assessment in the treatment of endometriosis.
The objective assessment of Danocrine (Danazol, Winthrop) in the treatment of endometriosis was hampered in the 1970s by the absence of a universally accepted classification. The American Fertility Society (AFS) classification, proposed in 1979, has now become widely accepted. However, there is a lack of recorded objective data utilizing the AFS score before and after Danazol therapy. In a series of 51 patients with endometriosis, who underwent laparoscopy, then received Danazol, 800 mg daily for 6 months, and had a repeat laparoscopy, there was a statistically significant improvement in the AFS score in Stage I and II disease.


Assessing the contribution of diazotrophs to microbial Fe uptake using a group specific approach in the Western Tropical South Pacific Ocean.
Diazotrophs are often limited by iron (Fe) availability in the oligotrophic ocean. The Western Tropical South Pacific (WTSP) ocean has been suggested as an intense N2 fixation area due to Fe fertilizations through shallow hydrothermal activity. Yet, the Fe demand of diazotrophs in their natural habitat, where they cohabit with other microbial organisms also requiring Fe, remains unknown. Here we develop and apply a method consisting of coupling 55Fe uptake experiments with cell-sorting by flow cytometry, and provide group-specific rates of in situ Fe uptake by the microbial community in the WTSP, in addition to bulk and size fractionation rates. We reveal that the diazotrophs Crocosphaera watsonii and Trichodesmium contribute substantially to the bulk in situ Fe uptake (~33% on average over the studied area), despite being numerically less abundant compared to the rest of the planktonic community. Trichodesmium had the highest cell-specific Fe uptake rates, followed by C. watsonii, picoeukaryotes, Prochlorococcus, Synechococcus and finally heterotrophic bacteria. Calculated Fe:C quotas were higher (by 2 to 52-fold) for both studied diazotrophs compared to those of the non-diazotrophic plankton, reflecting their high intrinsic Fe demand. This translates into a diazotroph biogeographical distribution that appears to be influenced by ambient dissolved Fe concentrations in the WTSP. Despite having low cell-specific uptake rates, Prochlorococcus and heterotrophic bacteria were largely the main contributors to the bulk Fe uptake (~23% and ~12%, respectively). Overall, this group-specific approach increases our ability to examine the ecophysiological role of functional groups, including those of less abundant and/or less active microbes.


[Case report of two work accidents investigated using the causal tree method]
In a large company in São Paulo State, two work accidents were investigated using the Causal Tree Method (CTM), leading to the accurate identification of factors related to work organization as the causal factors for the accidents. These cases pointed to the role of organizational factors, such as improvised and temporary assignments to work stations and/or jobs, decisions about the performance of tasks left to unprepared workers, unavailability of proper tools and/or materials, and faulty information distribution within the company. Analysis of the accidents allowed for the presentation and discussion of the method (CTM), its lengthy application, its demands in terms of training, and its potentialities for accident prevention.


Evolution of the transposable element mariner in Drosophila species.
The distribution of the transposable element mariner was examined in the genus Drosophila. Among the eight species comprising the melanogaster species subgroup, the element is present in D. mauritiana, D. simulans, D. sechellia, D. yakuba and D. teissieri, but it is absent in D. melanogaster, D. erecta and D. orena. Multiple copies of mariner were sequenced from each species in which the element occurs. The inferred phylogeny of the elements and the pattern of divergence were examined in order to evaluate whether horizontal transfer among species or stochastic loss could better account for the discontinuous distribution of the element among the species. The data suggest that the element was present in the ancestral species before the melanogaster subgroup diverged and was lost in the lineage leading to D. melanogaster and the lineage leading to D. erecta and D. orena. This inference is consistent with the finding that mariner also occurs in members of several other species subgroups within the overall melanogaster species group. Within the melanogaster species subgroup, the average divergence of mariner copies between species was lower than the coding region of the alcohol dehydrogenase (Adh) gene. However, the divergence of mariner elements within species was as great as that observed for Adh. We conclude that the relative sequence homogeneity of mariner elements within species is more likely a result of rapid amplification of a few ancestral elements than of concerted evolution. The mariner element may also have had unequal mutation rates in different lineages.


Eimeria tenella in gnotobiotic chickens: hematocrit, weight change, cecal pathology, and mortality.
On days 5 to 8 after oral inoculation with 200,000 Eimeria tenella oocysts, the mean hematocrits of bacteria-free, Bacillus cereus-monoflora and conventional chickens were equally reduced below control values. Weight loss was first observed in bacteria-free and monoflora fowl between days 4 and 5 after E. tenella inoculation, whereas conventional fowl initially displayed weight loss between days 3 and 4. Gross cecal lesion scores and total mortality of 4 experiments were not significantly different for the 2 gnotobiotic (bacteria-free and monoflora) groups, but these values for both groups were significantly less than those of infected conventional control animals. Since hematocrits were equally depressed in gnotobiotic and conventional animals, and survival was significantly greater in the former, it is suggested that factors in addition to blood loss cause mortality during E. tenella infections. The correlations between the severity of cecal lesions and per cent mortality suggests that these phenomena may be closely related. The present experiments with gnotobiotic fowl indicate that the normal flora is involved in the cecal pathology and mortality caused by cecal coccidiosis in conventional animals.


Fatal injury caused by low-energy trauma - a 10-year rural cohort.
Death after injury with low energy has gained increasing focus lately, and seems to constitute a significant amount of trauma-related death. The aim of this study was to describe the epidemiology of deaths from low-energy trauma in a rural Norwegian cohort. All deaths from external causes in Finnmark County, Norway, from 1995 to 2004 were identified retrospectively through the Norwegian Cause of Death Registry. Deaths caused by hanging, drowning, suffocation, poisoning, and electrocution were excluded. Trauma was categorised as high energy or low energy based on mechanism of injury. All low-energy trauma deaths were then reviewed. There were 262 cases of trauma death during the period. Low-energy trauma counted for 43% of the trauma deaths, with an annual crude death rate of 13 per 100,000 inhabitants. Low falls accounted for 99% of the injuries. Fractures were sustained in 89% of cases and head injuries in 11%. Ninety per cent of patients had pre-existing medical conditions, and the median age was 82 years. Death was caused by a medical condition in 85% of cases. Fifty-two per cent of the patients died after discharge from the hospital. In this cohort, low-energy trauma was a significant contributor to trauma related death, especially among elderly and patients with pre-existing medical conditions.


[Renal insufficiency due to interstitial nephritis in sarcoidosis].
The authors present their experience in diagnosing and treating interstitial nephritis with the development of chronic renal failure in a patient with generalized sarcoidosis, by involving the intrathoracic and peripheral lymph nodes, liver, spleen, subcutaneous fat, lung, as well as with the severe salivary and lachrymal gland lesions that imitate the clinical picture of Schogren's disease.


Natural hybridization and the evolution of domesticated, pest and disease organisms.
The role of natural hybridization in the evolutionary history of numerous species is well recognized. The impact of introgressive hybridization and hybrid speciation has been documented especially in plant and animal assemblages. However, there remain certain areas of investigation for which natural hybridization and its consequences remain under-studied and under-appreciated. One such area involves the evolution of organisms that positively or negatively affect human populations. In this review, I highlight exemplars of how natural hybridization has contributed to the evolution of (i) domesticated plants and animals; (ii) pests; (iii) human disease vectors; and (iv) human pathogens. I focus on the effects from genetic exchange that may lead to the acquisition of novel phenotypes and thus increase the beneficial or detrimental (to human populations) aspects of the various taxa.


A New Approach to Predict the Fish Fillet Shelf-Life in Presence of Natural Preservative Agents.
Three data sets concerning the behaviour of spoilage flora of fillets treated with natural preservative substances (NPS) were used to construct a new kind of mathematical predictive model. This model, unlike other ones, allows expressing the antibacterial effect of the NPS separately from the prediction of the growth rate. This approach, based on the introduction of a parameter into the predictive primary model, produced a good fitting of observed data and allowed characterising quantitatively the increase of shelf-life of fillets.


Inferring time series chromatin states for promoter-enhancer pairs based on Hi-C data.
Co-localized combinations of histone modifications ("chromatin states") have been shown to correlate with promoter and enhancer activity. Changes in chromatin states over multiple time points ("chromatin state trajectories") have previously been analyzed at promoter and enhancers separately. With the advent of time series Hi-C data it is now possible to connect promoters and enhancers and to analyze chromatin state trajectories at promoter-enhancer pairs. We present TimelessFlex, a framework for investigating chromatin state trajectories at promoters and enhancers and at promoter-enhancer pairs based on Hi-C information. TimelessFlex extends our previous approach Timeless, a Bayesian network for clustering multiple histone modification data sets at promoter and enhancer feature regions. We utilize time series ATAC-seq data measuring open chromatin to define promoters and enhancer candidates. We developed an expectation-maximization algorithm to assign promoters and enhancers to each other based on Hi-C interactions and jointly cluster their feature regions into paired chromatin state trajectories. We find jointly clustered promoter-enhancer pairs showing the same activation patterns on both sides but with a stronger trend at the enhancer side. While the promoter side remains accessible across the time series, the enhancer side becomes dynamically more open towards the gene activation time point. Promoter cluster patterns show strong correlations with gene expression signals, whereas Hi-C signals get only slightly stronger towards activation. The code of the framework is available at https://github.com/henriettemiko/TimelessFlex . TimelessFlex clusters time series histone modifications at promoter-enhancer pairs based on Hi-C and it can identify distinct chromatin states at promoter and enhancer feature regions and their changes over time.


Effect of Bisphosphonates, Denosumab, and Radioisotopes on Bone Pain and Quality of Life in Patients with Non-Small Cell Lung Cancer and Bone Metastases: A Systematic Review.
Bone metastases are common in patients with non-small cell lung cancer (NSCLC), often causing pain and a decrease in quality of life (QoL). The effect of bone-targeted agents is evaluated by reduction in skeletal-related events in which neither pain nor QoL are included. Radioisotopes can be administered for more diffuse bone pain that is not eligible for palliative radiotherapy. The evidence that bone-targeted agents relieve pain or improve QoL is not solid. We performed a systematic review of the effect of bone-targeted agents on pain and QoL in patients with NSCLC. Our systematic literature search included original articles or abstracts reporting on bisphosphonates, denosumab, or radioisotopes or combinations thereof in patients with bone metastases (≥5 patients with NSCLC), with pain, QoL, or both serving as the primary or secondary end point. Of the twenty-five eligible studies, 13 examined bisphosphonates (one also examined denosumab) and 12 dealt with radioisotopes. None of the randomized studies on bisphosphonates or denosumab evaluated pain and QoL as the primary end point. In the single-arm studies of bisphosphonates a decrease in pain or analgesic consumption was found for 38% to 77% of patients. QoL was included in five of 13 studies, but improvement was found in only two. No high-level evidence that bisphosphonates or denosumab reduce pain or improve QoL was found. Although the data are limited, radioisotopes seem to reduce pain with a rapid onset of action and duration of response of 1 to 3 months. The evidence that bisphosphonates or denosumab reduce or prevent pain in patients with NSCLC and bone metastases or that they have an influence on QoL is very weak. Radioisotopes can be used to reduce diffuse pain, although there is no high-level evidence supporting such use.


Complete workplace indoor smoking ban and smoking behavior among male workers and female nonsmoking workers' husbands: a pseudo cohort study of Japanese public workers.
A pseudo cohort study using national cross-sections (2001, 2004, 2007, and 2010) was conducted to examine differences in smoking prevalence under different smoking ban policies such as a complete workplace indoor smoking ban (early or recent implementation) and a partial smoking ban among male public workers and husbands of female nonsmoking public workers. The effectiveness of smoking bans was estimated by difference-in-differences (DID) with age group stratification. The results varied considerably by age and implementation period. Although DID estimates (positive value of DID estimate represents smoking cessation percentage) for both smoking bans on total male smoking were not significant, the over-40 age group indicated a significant DID estimate of 5.0 (95% CI: 0.2, 9.8) for the recent smoking ban. For female workers' husbands' smoking, the over-40 age group indicated positive, but not significant, DID estimates for the early and recent smoking bans of 7.2 (-4.7, 19.2) and 8.4 (-2.0, 18.7), respectively. A complete indoor workplace smoking ban, particularly one recently implemented among public office workers aged over 40, may reduce male workers' smoking and female workers' husbands' smoking compared with a partial smoking ban, but the conclusion remains tentative because of methodological weaknesses in the study.


NFKB1 rs28362491 and pre-miRNA-146a rs2910164 SNPs on E-Cadherin expression in case of idiopathic oligospermia: A case-control study.
A notable proportion of idiopathic male infertility cases is accompanied by oligozoospermia; and yet, the molecular mechanisms of fertilization problem underlying this defect are still unclear. Epithelial cadherin has been involved in several calcium-dependent cell-to-cell adhesion events; however, its participation in gamete interaction has also not been fully investigated. The aim was to investigate the changes in the expression of E-cadherin, based on the frequency of Single nucleotide polymorphisms in Nuclear Factor Kappa-B 1 and pre-mir-146a in oligospermic men. In this case-control study, semen and blood samples of 131 oligospermic men as the case group and 239 fertile healthy men as the control group were analyzed. Variants single nucleotide polymorphisms rs28362491 and rs2910164 were performed using polymerase chain reaction-restriction fragment length polymorphism method and E-cadherin expression were determined by immunoprecipitation studies. ins/ins genotype of rs28362491 was determined as a risk factor for idiopathic oligospermia by 1.73 times (p=0.0218), whereas no significant differences were found between the groups concerning pre-mir-146a rs2910164 polymorphism (p=0.2274 in case of GC genotype and p=0.9052 in case of GG genotype). Combined genotype analysis results did not show any notable differences between the multiple comparisons of 28362491-rs2910164 in oligospermic men and control groups. In addition, E-cadherin expression of oligospermic men with ins/ins genotype was significantly lower than patients with del/ins genotype (p=0.0221). E-cadherin expression level was low in oligospermic men with respect to the control group in presence of ins/ins genotype of NFKB1 gene. These results suggest that ins allele prevents binding of surface proteins to spermatozoa, leading to a low affinity of sperm-oocyte interaction in oligospermic men.


Hb Q(India) and its interaction with beta-thalassaemia: a study of 64 cases from India.
Haemoglobin Q (Hb Q), a relatively uncommon alpha-chain structural Hb variant, has been reported either in the heterozygous state or interacting with beta-thalassaemia. Individuals inheriting Hb Q generally are asymptomatic and are diagnosed by chance during population screening or as a part of a family study. This paper represents the first large study from India of 64 cases of Hb Q, documenting the haematological and molecular findings on 36 cases of Hb Q trait, 22 of Hb Q beta-thalassaemia trait and three of Hb Q beta-thalassaemia major, as well as a family of Hb Q homozygous cases. Hb Q is detected by Hb electrophoresis and chromatography. Hb Q levels in homozygous cases ranged from 32% to 35%, while in Hb Q heterozygotes the level was 20%. When there was an interaction of beta-thalassaemia heterozygotes the level was 14%, and in interacting beta-thalassaemia homozygotes the levels ranged from 7% to 9%. beta-thalassaemia mutations were characterised in cases showing elevated Hb A2 levels, which were markedly reduced in the majority of cases in which beta-thalassaemia was absent. Hb Q is rare and not a single homozygous case has been reported. However, Hb Q disease showed wide variation in clinical and haematological presentation in the same family.


Tocopherol in Osteoarthritis: a controlled pilot study.
Thirty-two patients entered a simple-blind, cross-over study on the action of tocopherol in osteoarthritis; only 3 did not complete the course. Each patient was randomly assigned either to the tocopherol group (600 mg/day for 10 days) or to the placebo group. After 10 days the groups were transposed. The analgesic and other possible effects of tocopherol vs. placebo were assessed by the patients' daily records, by the physician's personal examination and interview, and by observations on the use of an additionally permitted analgesic (pro re nata). In 52 percent of the 29 patients who completed the study of good tocopherol analgesic effect was noted, but only 4 percent of those receiving placebo reported a similar effect. The difference was statistically significant. Further large-scale assessement of the influence of tocopherol in osteoarthritis would seem to be justified.


Neural correlates of observing pretend play in which one object is represented as another.
Observers were scanned while they watched a video of an actor using an object. Three conditions were contrasted in which the same object was used: (i) normally (e.g. using a tennis racket to hit a ball), (ii) in an unusual way (e.g. using a tennis racket to strain spaghetti), (iii) in a pretend play (e.g. playing a tennis racket like a banjo). Observing real and unusual uses of objects activated areas previously seen in studies of tool use including areas associated with a mirror system for action. Observing pretend play activated additional areas previously associated with theory of mind tasks and listening to narrative, including medial prefrontal cortex, posterior superior temporal sulcus and temporal poles. After presentation of each video, observers were asked to name the object as used in the preceding action video (e.g. racket, sieve or banjo). Naming the pretend object elicited activity in medial prefrontal cortex. These results are consistent with proposals that pretend play is a form of communicative narrative, associated with the ability to mentalize. However, this leaves open the question as to whether pretence or mentalizing is the more basic process.


Sox2 regulates cholinergic amacrine cell positioning and dendritic stratification in the retina.
The retina contains two populations of cholinergic amacrine cells, one positioned in the ganglion cell layer (GCL) and the other in the inner nuclear layer (INL), that together comprise ∼1/2 of a percent of all retinal neurons. The present study examined the genetic control of cholinergic amacrine cell number and distribution between these two layers. The total number of cholinergic amacrine cells was quantified in the C57BL/6J and A/J inbred mouse strains, and in 25 recombinant inbred strains derived from them, and variations in their number and ratio (GCL/INL) across these strains were mapped to genomic loci. The total cholinergic amacrine cell number was found to vary across the strains, from 27,000 to 40,000 cells, despite little variation within individual strains. The number of cells was always lower within the GCL relative to the INL, and the sizes of the two populations were strongly correlated, yet there was variation in their ratio between the strains. Approximately 1/3 of that variation in cell ratio was mapped to a locus on chromosome 3, where Sex determining region Y box 2 (Sox2) was identified as a candidate gene due to the presence of a 6-nucleotide insertion in the protein-coding sequence in C57BL/6J and because of robust and selective expression in cholinergic amacrine cells. Conditionally deleting Sox2 from the population of nascent cholinergic amacrine cells perturbed the normal ratio of cells situated in the GCL versus the INL and induced a bistratifying morphology, with dendrites distributed to both ON and OFF strata within the inner plexiform layer.


[The application of the endovascular prosthesis (stent)].
We report two cases of symptomatic internal carotid stenosis treated by vasoplasty and stent placement in two male patients aged 57 and 64 years, one who had been suffering from transient ischemic events and the other had had a recent cerebral infarction with hemiparesis. The treatment sessions took place without complications. We discuss the choice of simultaneous vasoplasty and stent placement, some of the current possible indications for the method and the importance of multidisciplinary planning for the patient's evaluation and treatment.


Dual RNA-seq reveals a type 6 secretion system-dependent blockage of TNF-α signaling and BicA as a Burkholderia pseudomallei virulence factor important during gastrointestinal infection.
Melioidosis is a disease caused by the Gram-negative bacillus Burkholderia pseudomallei (Bpm), commonly found in soil and water of endemic areas. Naturally acquired human melioidosis infections can result from either exposure through percutaneous inoculation, inhalation, or ingestion of soil-contaminated food or water. Our prior studies recognized Bpm as an effective enteric pathogen, capable of establishing acute or chronic gastrointestinal infections following oral inoculation. However, the specific mechanisms and virulence factors involved in the pathogenesis of Bpm during intestinal infection are unknown. In our current study, we standardized an in vitro intestinal infection model using primary intestinal epithelial cells (IECs) and demonstrated that Bpm requires a functional T6SS for full virulence. Further, we performed dual RNA-seq analysis on Bpm-infected IECs to evaluate differentially expressed host and bacterial genes in the presence or absence of a T6SS. Our results showed a dysregulation in the TNF-α signaling via NF-κB pathway in the absence of the T6SS, with some of the genes involved in inflammatory processes and cell death also affected. Analysis of the bacterial transcriptome identified virulence factors and regulatory proteins playing a role during infection, with association to the T6SS. By using a Bpm transposon mutant library and isogenic mutants, we showed that deletion of the bicA gene, encoding a putative T3SS/T6SS regulator, ablated intracellular survival and plaque formation by Bpm and impacted survival and virulence when using murine models of acute and chronic gastrointestinal infection. Overall, these results highlight the importance of the type 6 secretion system in the gastrointestinal pathogenesis of Bpm.


Translation of artemether-lumefantrine treatment policy into paediatric clinical practice: an early experience from Kenya.
To describe the quality of outpatient paediatric malaria case-management approximately 4-6 months after artemether-lumefantrine (AL) replaced sulfadoxine-pyrimethamine (SP) as the nationally recommended first-line therapy in Kenya. Cross-sectional survey at all government facilities in four Kenyan districts. Main outcome measures were health facility and health worker readiness to implement AL policy; quality of antimalarial prescribing, counselling and drug dispensing in comparison with national guidelines; and factors influencing AL prescribing for treatment of uncomplicated malaria in under-fives. We evaluated 193 facilities, 227 health workers and 1533 sick-child consultations. Health facility and health worker readiness was variable: 89% of facilities stocked AL, 55% of health workers had access to guidelines, 46% received in-service training on AL and only 1% of facilities had AL wall charts. Of 940 children who needed AL treatment, AL was prescribed for 26%, amodiaquine for 39%, SP for 4%, various other antimalarials for 8% and 23% of children left the facility without any antimalarial prescribed. When AL was prescribed, 92% of children were prescribed correct weight-specific dose. AL dispensing and counselling tasks were variably performed. Higher health worker's cadre, in-service training including AL use, positive malaria test, main complaint of fever and high temperature were associated with better prescribing. Changes in clinical practices at the point of care might take longer than anticipated. Delivery of successful interventions and their scaling up to increase coverage are important during this process; however, this should be accompanied by rigorous research evaluations, corrective actions on existing interventions and testing cost-effectiveness of novel interventions capable of improving and maintaining health worker performance and health systems to deliver artemisinin-based combination therapy in Africa.


Productive Infection of Mouse Mammary Glands and Human Mammary Epithelial Cells by Zika Virus.
Zika virus (ZIKV) belongs to the large category of arboviruses. Surprisingly, several human-to-human transmissions of ZIKV have been notified, either following sexual intercourse or from the mother to fetus during pregnancy. Importantly, high viral loads have been detected in the human breast milk of infected mothers, and the existence of breastfeeding as a new mode of mother-to-child transmission of ZIKV was recently hypothesized. However, the maternal origin of infectious particles in breast milk is currently unknown. Here, we show that ZIKV disseminates to the mammary glands of infected mice after both systemic and local exposure with differential kinetics. Ex vivo, we demonstrate that primary human mammary epithelial cells were sensitive and permissive to ZIKV infection in this study. Moreover, by using in vitro models, we prove that mammary luminal- and myoepithelial-phenotype cell lines are both able to produce important virus progeny after ZIKV exposure. Our data suggest that the dissemination of ZIKV to the mammary glands and subsequent infection of the mammary epithelium could be one mechanism of viral excretion in human breast milk.


Seattle's sweetened beverage tax implementation and changes in interior marketing displays.
Policymakers aim sugar-sweetened beverage (SSB) taxes at decreasing SSB consumption; however, little is known about their impact on beverage marketing in the retail environment. We assessed changes in interior marketing displays within large food stores before and after the implementation of Seattle's SSB tax. We used Poisson difference-in-difference (DID) models to estimate whether presence and variety of interior beverage marketing displays in Seattle changed from before to after the tax compared to displays in non-taxed comparison area stores, overall, and by beverage type. We found no significant changes in overall SSB or non-SSB interior marketing displays in Seattle versus the comparison area. There was less of an increase in displays for diet soda (DID 0.79, 90% CI 0.65, 0.97), and more of an increase in displays for diet energy drinks (DID 1.78, 90% CI 1.03, 3.09) in Seattle versus comparison area. There was mixed evidence that stores changed interior marketing displays in response to the SSB tax.


Quality of life and the associated factors among family caregivers of older people with dementia in Thailand.
Long-term care for older people with dementia can adversely impact a family caregiver's life. A decrease in their quality of life may compromise the quality of care they provide to older people and their own quality of life. The samples include 76 family caregivers of older people with dementia in Thailand. Six questionnaires and the EuroQoL Five Dimensions Questionnaire were used in data collection. Descriptive and inferential statistics were used in data analysis. The findings revealed that quality of life of family caregivers was at a high level. Experiences of close relationships between care dyads and perceived social support were positively related to family caregiver's quality of life, whereas perceived stress and burden were negatively related. Perceived social support and experiences of close relationships might be predictors of family caregiver's quality of life. High quality of life levels among Thai family caregivers of older people with dementia were influenced by high perceived social support and high experiences of close relationships. An intervention focusing on modifying such predicting factors may effectively help maintain quality of life of these family caregivers.


Exploring high school learners' perceptions of bullying.
Learners' perceptions of aspects of school life that are sufficiently serious to interfere with their schoolwork were investigated. Bullying was a form of behaviour that was singled out for inclusion and further exploration in the study. Learners from three coeducational Western Cape Education Department schools were surveyed: 414 Grade 8 and 474 Grade 9 learners completed an anonymous, voluntary self-report questionnaire. Factors identified as most frequently interfering with their schoolwork included classmates not listening in class, feeling overwhelmed by schoolwork, teacher absenteeism, and verbal fighting. When asked specifically about bullying, 40% of learners indicated that they frequently experienced bullying at school-although they ranked it as much lower when compared to other potentially problematic school experiences. Furthermore, although the majority of learners indicated they thought teachers considered bullying a problem, few felt there was anything that school staff could do to counteract bullying effectively. These findings suggest that learners perceive bullying as an unavoidable part of school experience and have normalised this aggressive behaviour.


A unified architecture of transcriptional regulatory elements.
Gene expression is precisely controlled in time and space through the integration of signals that act at gene promoters and gene-distal enhancers. Classically, promoters and enhancers are considered separate classes of regulatory elements, often distinguished by histone modifications. However, recent studies have revealed broad similarities between enhancers and promoters, blurring the distinction: active enhancers often initiate transcription, and some gene promoters have the potential to enhance transcriptional output of other promoters. Here, we propose a model in which promoters and enhancers are considered a single class of functional element, with a unified architecture for transcription initiation. The context of interacting regulatory elements and the surrounding sequences determine local transcriptional output as well as the enhancer and promoter activities of individual elements.


Natural constituents from food sources: potential therapeutic agents against muscle wasting.
Skeletal muscle wasting is highly correlated with not only reduced quality of life but also higher morbidity and mortality. Although an increasing number of patients are suffering from various kinds of muscle atrophy and weakness, there is still no effective therapy available, and skeletal muscle is considered as an under-medicated organ. Food provided not only essential macronutrients but also functional substances involved in the modulation of the physiological systems of our body. Natural constituents from commonly consumed dietary plants, either extracts or compounds, have attracted more and more attention to be developed as agents for preventing and treating muscle wasting due to their safety and effectiveness, as well as structural diversity. This review provides an overview of the mechanistic aspects of muscle wasting, and summarizes the extracts and compounds from food sources as potential therapeutic agents against muscle wasting.


High incidence of noninfectious esophagitis in orthotopic liver transplant (OLT) recipients.
Incidence of esophagitis among cirrhotics is similar to the general population; post-OLT course of this entity is not well known. The aim of this study was to assess the incidence of non-infectious esophagitis among OLT recipients. Patients with chronic liver disease who have been considered for transplantation have undergone esophagogastroduodenoscopy (EGD) for examination of the upper gastrointestinal tract. Following transplantation, some of these patients have required EGD for various reasons. EGD findings following transplantation were compared to that individual's pre-transplant findings. There were 173 patients and the median age was 49. The incidence of pre-transplant esophagitis was 7.5%, which increased to 22% after OLT (p > 0.0001). None had specific etiology. Etiology of this increase needs to be further investigated and the effects of immunosuppressive drugs on lower esophageal sprinter and gastric motility should be clarified. Use of acid suppressing drugs during the early post-transplant period should be considered.


Mental illness self-management: a randomised controlled trial of the Wellness Recovery Action Planning intervention for inpatients and outpatients with psychiatric illness.
Wellness Recovery Action Planning (WRAP) is a cross-diagnostic, patient-centred, self-management intervention for psychiatric illness. WRAP utilises an individualised Wellness Toolbox, a six part structured monitoring and response system, and a crisis and post-crisis plan to promote recovery. The objective of this study was to evaluate the effect of WRAP on personal recovery, quality of life, and self-reported psychiatric symptoms. A prospective randomised controlled trial, based on the CONSORT principles was conducted using a sample of 36 inpatients and outpatients with a diagnosis of a mental disorder. Participants were randomly allocated to Experimental Group or Waiting List Control Group conditions in a 1:1 ratio. Measures of personal recovery, personal recovery life areas, quality of life, anxiety, and depression were administered at three time points: (i) pre-intervention, (ii) post-Experimental Group intervention delivery, and (iii) 6-month follow-up. Data was analysed by available case analysis using univariate and bivariate methodologies. WRAP had a significant effect on two personal recovery life areas measured by the Mental Health Recovery Star: (i) addictive behaviour and (ii) identity and self-esteem. WRAP did not have a significant effect on personal recovery (measured by the Mental Health Recovery Measure), quality of life, or psychiatric symptoms. Findings indicate that WRAP improves personal recovery in the areas of (i) addictive behaviour and (ii) identity and self-esteem. Further research is required to confirm WRAP efficacy in other outcome domains. Efforts to integrate WRAP into recovery-orientated mental health services should be encouraged and evaluated.


[The role of neurotrophic factors in formation of vibration disease].
The authors studied serum levels of neurotrophic factors (brain-derived neurotrophic factor BDNF and ciliary neurotrophic factor CNTF) in workers exposed to vibration (workers with long length of service and without health disorders caused by vibration, patients with occupational limbs polyneuropathy, and vibration disease patients). Findings are that occupational vibration induces increased BDNF and CNTF serum levels in all groups examined. Increased levels of neurotrophic factors at early stages of pathologic process indicate their protective action, action of compensatory protective mechanisms. However, high levels of BDNF and CNTF in vibration disease may point to neurodestructive processes in nervous system.


Continuous Magnesium Infusion to Prevent Atrial Fibrillation After Cardiac Surgery: A Sequential Matched Case-Controlled Pilot Study.
The authors aimed to test whether a bolus of magnesium followed by continuous intravenous infusion might prevent the development of atrial fibrillation (AF) after cardiac surgery. Sequential, matched, case-controlled pilot study. Tertiary university hospital. Matched cohort of 99 patients before and intervention cohort of 99 consecutive patients after the introduction of a continuous magnesium infusion protocol. The magnesium infusion protocol consisted of a 10 mmol loading dose of magnesium sulphate followed by a continuous infusion of 3 mmol/h over a maximum duration of 96 hours or until intensive care unit discharge. The study groups were balanced except for a lower cardiac index in the intervention cohort. The mean duration of magnesium infusion was 27.93 hours (95% confidence interval [CI]: 24.10-31.76 hours). The intervention group had greater serum peak magnesium levels: 1.72 mmol/L ± 0.34 on day 1, 1.32 ± 0.36 on day 2 versus 1.01 ± 1.14 and 0.97 ± 0.13, respectively, in the control group (p < 0.01). Atrial fibrillation occurred in 25 patients (25.3%) in the intervention group and 40 patients (40.4%) in the control group (odds ratio 0.49, 95% CI, 0.27-0.92; p = 0.023). On a multivariate Cox proportional hazards model, the hazard ratio for the development of AF was significantly less in the intervention group (hazard ratio 0.45, 95% CI, 0.26-0.77; p = 0.004). The magnesium delivery strategy was associated with a decreased incidence of postoperative AF in cardiac surgery patients. These findings provide a rationale and preliminary data for the design of future randomized controlled trials.


Post-Soviet transition: improving health services delivery and management.
During the post-Soviet transition of the last 2 decades, ex-Communist countries of the Eastern Bloc, including eastern and central Europe, the Soviet Union, and its satellite and aligned states, have undergone major health system reforms. Many health systems of those countries--previously adopting a Soviet-type Semashko model--are currently called "in transition," as reform agendas, such as shifting to a Bismarck, Beveridge, or mixed financing scheme or adopting new health delivery management policies, are still in development. In this article, we first review common characteristics of Semashko health systems (the predominant health system of Communist countries during the Soviet era) and then discuss the "new public management" principles that ex-Communist countries have recently started to adopt with various degrees of success. We then illustrate experiences with these principles using 2 case studies, from Russia and Albania, and propose health policy options for both cases. Based on a review of the literature and on the our work experience in Russia and Albania, we found that the 2 ex-Semashko systems have not fully capitalized on expected positive outcomes of new public management principles due to low local healthcare financing levels, depreciated healthcare infrastructure and operational capacities, overlapping and contradicting ideology and policies of the former and newer health systems, and finally, lack of leadership that has successful experience with these principles. In the case of pharmaceutical pricing, reimbursement, and access in Russia, we show how a well-intentioned but suboptimally designed and managed pharmaceutical coverage scheme has suffered moral hazard and adverse selection and has adversely impacted the new public management promise of efficient medicine coverage. In the case of Albania, the delayed investment in human resource reform within a depreciated and underfinanced delivery system has adversely affected the implementation of new public management principles.


Hepatic encephalopathy.
Hepatic encephalopathy (HE) is a reversible syndrome of impaired brain function occurring in patients with advanced liver diseases. The precise pathophysiology of HE is still under discussion; the leading hypothesis focus on the role of neurotoxins, impaired neurotransmission due to metabolic changes in liver failure, changes in brain energy metabolism, systemic inflammatory response and alterations of the blood brain barrier. HE produces a wide spectrum of nonspecific neurological and psychiatric manifestations. Minimal HE is diagnosed by abnormal psychometric tests. Clinically overt HE includes personality changes, alterations in consciousness progressive disorientation in time and space, somnolence, stupor and, finally, coma. Except for clinical studies, no specific tests are required for diagnosis. HE is classified according to the underlying disease, the severity of manifestations, its time course and the existence of precipitating factors. Treatment of overt HE includes supportive therapies, treatment of precipitating factors, lactulose and/or rifaximin. Routine treatment for minimal HE is only recommended for selected patients.


Smoking cessation.
Cigarette smoking is the primary cause of chronic obstructive pulmonary disease, and smoking cessation is the most effective means of stopping the progression of chronic obstructive pulmonary disease. Worldwide, approximately a billion people smoke cigarettes and 80% reside in low-income and middle-income countries. Though in the United States there has been a substantial decline in cigarette smoking since 1964, when the Surgeon General's report first reviewed smoking, smoking remains widespread in the United States today (about 23% of the population in 2001). Nicotine is addictive, but there are now effective drugs and behavioral interventions to assist people to overcome the addiction. Available evidence shows that smoking cessation can be helped with counseling, nicotine replacement, and bupropion. Less-studied interventions, including hypnosis, acupuncture, aversive therapy, exercise, lobeline, anxiolytics, mecamylamine, opioid agonists, and silver acetate, have assisted some people in smoking cessation, but none of those interventions has strong research evidence of efficacy. To promote smoking cessation, physicians should discuss with their smoking patients "relevance, risk, rewards, roadblocks, and repetition," and with patients who are willing to attempt to quit, physicians should use the 5-step system of "ask, advise, assess, assist, and arrange." An ideal smoking cessation program is individualized, accounting for the reasons the person smokes, the environment in which smoking occurs, available resources to quit, and individual preferences about how to quit. The clinician should bear in mind that quitting smoking can be very difficult, so it is important to be patient and persistent in developing, implementing, and adjusting each patient's smoking-cessation program. One of the most effective behavioral interventions is advice from a health care professional; it seems not to matter whether the advice is from a doctor, respiratory therapist, nurse, or other clinician, so smoking cessation should be encouraged by multiple clinicians. However, since respiratory therapists interact with smokers frequently, we believe it is particularly important for respiratory therapists to show leadership in implementing smoking cessation.


Estimation of multiple networks in Gaussian mixture models.
We aim to estimate multiple networks in the presence of sample heterogeneity, where the independent samples (i.e. observations) may come from different and unknown populations or distributions. Specifically, we consider penalized estimation of multiple precision matrices in the framework of a Gaussian mixture model. A major innovation is to take advantage of the commonalities across the multiple precision matrices through possibly nonconvex fusion regularization, which for example makes it possible to achieve simultaneous discovery of unknown disease subtypes and detection of differential gene (dys)regulations in functional genomics. We embed in the EM algorithm one of two recently proposed methods for estimating multiple precision matrices in Gaussian graphical models. We demonstrate the feasibility and potential usefulness of the proposed methods in an application to glioblastoma subtype discovery and differential gene network analysis with a microarray gene expression data set. We also conduct realistic simulation studies to evaluate and compare the performance of various methods.


[Antibodies anti granulocytic antigens in IBD: from microscopic morphology to antigenic specificity].
ANCA (p-ANCA and x-ANCA) have been documented to occur in many inflammatory disorders. The specific ANCA antigens and the clinical correlation of a positive ANCA test in these disorders are still for the most part obscure. The aim of the present study was to investigate the prevalence of and the target antigens for ANCA in patients with IBD. 104 patients (67 age between 3-18 years, mean age 8+/-3 and 37 age between 25-70 years, mean age 48+/-15) clinically and hystopathologically diagnosed as: 67 ulcerative colitis, 16 Crohn' disease, 21 other colitis (7 indeterminate colitis) were enrolled in our study. ANCA were determined by ELISA and IIF methods. We observed a good performance in terms of sensibility and specificity of ANCA, and a good correlation between the two methods used; as regard ELISA determination the antigen frequently found in our cases was lactoferrin (60%). Is still unclear the role of these "minor antigens" in the diagnosis and pathogenesis of IBD, but is clear that only morphologic evaluation is no more sufficient.


Impact of in-feed sodium butyrate or sodium heptanoate protected with medium-chain fatty acids on gut health in weaned piglets challenged with Escherichia coli F4.
Short and medium-chain fatty acids (SCFA and MCFA, respectively) are commonly used as feed additives in piglets to promote health and prevent post-weaning diarrhoea. Considering that the mechanism and site of action of these fatty acids can differ, a combined supplementation could result in a synergistic action. Considering this, it was aimed to assess the potential of two new in-feed additives based on butyrate or heptanoate, protected with sodium salts of MCFA from coconut distillates, against enterotoxigenic Escherichia coli (ETEC) F4+ using an experimental disease model. Two independent trials were performed in 48 early-weaned piglets fed a control diet (CTR) or a diet supplemented with MCFA-protected sodium butyrate (BUT+; Trial 1) or sodium heptanoate (HPT+; Trial 2). After 1 week of adaptation, piglets were challenged with a single oral inoculum of ETEC F4+ (minimum 1.4 · 109 cfu). One animal per pen was euthanised on days 4 and 8 post-inoculation (PI) and the following variables assessed: growth performance, clinical signs, gut fermentation, intestinal morphology, inflammatory mediators, pathogen excretion and colon microbiota. None of the additives recovered growth performance or reduced diarrhoea when compared to the respective negative controls. However, both elicited different responses against ETEC F4+. The BUT+ additive did not lead to reduce E. coli F4 colonisation but enterobacterial counts and goblet cell numbers in the ileum were increased on day 8 PI and this followed higher serum TNF-α concentrations on day 4 PI. The Firmicutes:Bacteroidetes ratio was nevertheless increased. Findings in the HPT+ treatment trial included fewer animals featuring E. coli F4 in the colon and reduced Enterobacteriaceae (determined by 16S RNA sequencing) on day 4 PI. In addition, while goblet cell numbers were lower on day 8 PI, total SCFA levels were reduced in the colon. Results indicate the efficacy of MCFA-protected heptanoate against ETEC F4+ and emphasise the potential trophic effect of MCFA-protected butyrate on the intestinal epithelium likely reinforcing the gut barrier.


[Mechanisms and dynamics of drug resistance in Plasmodium falciparum].
The emergence of chloroquine resistance has been associated with a dramatic increase in malaria mortality in some human populations from endemic regions. Plasmodium falciparum drug resistant malaria originates from chromosomal mutations. Analysis using molecular, genetic and biochemical approaches has shown that 1) impaired intake of chloroquine by the parasite vacuole is a common characteristic of resistant strains, the chloroquine-resistance mechanism regulates the access of chloroquine to hematin, this phenotype correlates with Pfmdr1 and Pfcg2 gene mutations; 2) one to four point mutations of dihydrofolate reductase, the enzyme target of antifolinics (pyrimethamine and proguanil), give moderate to high levels of resistance to these drugs but there is a fitness cost to resistance; 3) the mechanism of resistance to sulfonamides and sulfones involves mutations of dihydropteroate synthase, their enzyme target; 4) treatment with sulphadoxine-pyrimethamine (SP) selected for the variants Ile(51), Arg(59) and Asn(108) of DHFR and for the variants Ser(436), Gly(437), and Glu(540) of DHPS; 5)clones that were resistant to some traditional antimalarial agents acquired resistance to new ones at high frequency (accelerated resistance to multiple drugs--ARMD). Amino-alcohol (quinine, mefloquine, halofantrine) mechanisms of resistance are still unclear. Population genetic studies have confirmed that selfing is more frequent in Plasmodium falciparum where the transmission rate is lower in some regions such as Papua-New Guinea, whereas isolates from individuals on the Thai-Burmese border, an area of hypoendemic transmission, revealed a higher number of genotypes per infected person. It has been suggested that intense intra-host competition between co-infecting clones, low numbers of genes required to encode resistance, and high drug usage all encourage the emergence of drug resistance. On the other hand, the greater effective recombination in high transmission areas may breakdown multiple drug resistance when it is coded for by two unlinked loci. Epidemiological studies have established that the frequency of chloroquine resistant mutants varies among parasite isolate populations while resistance to antifolinics is highly prevalent in most malarial endemic countries (more than 92% of Kenyan field isolates have undergone at least one point mutation). Established and strong drug pressure as well as low antiparasitic immunity probably explains the multidrug-resistance encountered in forests of Southeast Asia and South America. In Africa, frequent genetic recombinations in Plasmodium originate from a high level of malaria transmission, and falciparum chloroquine-resistant prevalence seems to stabilise at an equal level as chloroquine-sensitive malaria. Clinical studies demonstrated that control of clinical symptoms is better when chloroquine is used with sulphadoxine-pyrimethamine (SP) than when SP is used alone, and the cure rate also tends to be higher with the triple combination regimen.


A prospective study on time to recovery in 254 injured novice runners.
Describe the diagnoses and the time to recovery of running-related injuries in novice runners. Prospective cohort study on injured runners. This paper is a secondary data analysis of a 933-person cohort study (DANO-RUN) aimed at characterizing risk factors for injury in novice runners. Among those sustaining running-related injuries, the types of injuries and time to recovery is described in the present paper. All injured runners were diagnosed after a thorough clinical examination and then followed prospectively during their recovery. If they recovered completely from injury, time to recovery of each injury was registered. A total of 254 runners were injured. The proportion of runners diagnosed with medial tibial stress syndrome was 15%, 10% for patellofemoral pain, 9% for medial meniscal injury, 7% for Achilles tendinopathy and 5% for plantar fasciitis. Among the 220 runners (87%) recovering from their injury, the median time to recovery was 71 days (minimum = 9 days, maximum = 617 days). Medial tibial stress syndrome was the most common injury followed by patellofemoral pain, medial meniscal injury and Achilles tendinopathy. Half of the injured runners were unable to run 2×500 meters without pain after 10 weeks. Almost 5% of the injured runners received surgical treatment.


[Complete Surgical Resection for Lung Cancer Invading Anterior Apex after Preoperative Chemoradiotherapy Via Transmanubrial Approach and Anterolateral Thoracotomy].
Surgical resection plays an important role as a radical treatment for lung cancers. Many lung cancer patients are found in an advanced state and it is currently in a condition that can not be operated, and the prognosis is also bad. For locally advanced lung cancer, complete resection including surrounding organs is expected by performing chemoradiotherapy before surgery. We report a case of complete surgical resection for lung cancer invading anterior apex after preoperative chemoradiotherapy via transmanubrial approach and anterolateral thoracotomy.


A comparative genomics study of 23 Aspergillus species from section Flavi.
Section Flavi encompasses both harmful and beneficial Aspergillus species, such as Aspergillus oryzae, used in food fermentation and enzyme production, and Aspergillus flavus, food spoiler and mycotoxin producer. Here, we sequence 19 genomes spanning section Flavi and compare 31 fungal genomes including 23 Flavi species. We reassess their phylogenetic relationships and show that the closest relative of A. oryzae is not A. flavus, but A. minisclerotigenes or A. aflatoxiformans and identify high genome diversity, especially in sub-telomeric regions. We predict abundant CAZymes (598 per species) and prolific secondary metabolite gene clusters (73 per species) in section Flavi. However, the observed phenotypes (growth characteristics, polysaccharide degradation) do not necessarily correlate with inferences made from the predicted CAZyme content. Our work, including genomic analyses, phenotypic assays, and identification of secondary metabolites, highlights the genetic and metabolic diversity within section Flavi.


Local Infiltration Analgesia for Postoperative Pain Control following Total Hip Arthroplasty: A Systematic Review.
Local infiltration analgesia (LIA) is an analgesic technique that has gained popularity since it was first brought to widespread attention by Kerr and Kohan in 2008. The technique involves the infiltration of a large volume dilute solution of a long-acting local anesthetic agent, often with adjuvants (e.g., epinephrine, ketorolac, an opioid), throughout the wound at the time of surgery. The analgesic effect duration can then be prolonged by the placement of a catheter to the surgical site for postoperative administration of further local anesthetic. The technique has been adopted for use for postoperative analgesia following a range of surgical procedures (orthopedic, general, gynecological, and breast surgeries). The primary objective of this paper was to determine, based on the current evidence, if LIA is superior when compared to no intervention, placebo, and alternative analgesic methods in patients following total hip arthroplasty, in terms of certain outcome measures. The outcomes considered were postoperative analgesia scores, joint function/rehabilitation, and length of hospital stay. Secondary objectives were to review available evidence and current knowledge regarding the pharmacokinetics of local anesthetic and adjuvant drugs when administered in this way and the occurrence of adverse events.


Investigating the Link between Later-Life Brain Volume and Cardiorespiratory Fitness after Mild Traumatic Brain Injury Exposure.
Evidence suggests that maintaining a higher level of cardiorespiratory fitness (CRF) later in life can offer some protection against brain volume loss as we age. By contrast, mild traumatic brain injury (mTBI) could accelerate age-related cortical atrophy. The current study sought to examine whether variations in the CRF level modified the association between mTBI history and brain volumetric measures in a sample of older adults. Seventy-nine community-dwelling older adults (mean age 68.7 ± 4.3 years, 54.4% female) were assessed for their mTBI history: 25 participants (32%) reported sustaining at least one lifetime mTBI. Participants also underwent a CRF assessment and magnetic resonance imaging (MRI) to obtain global and region-of-interest volumes. Analysis of covariance, controlling for age, sex, education, and apolipoprotein (APOE) ε4 allele carriage, revealed that participants with a history of mTBI had a significantly larger total mean grey matter volume (582.21 ± 12.46 cm3) in comparison to participants with no mTBI history (571.08 ± 17.21 cm3, p = 0.01 after correction for multiple comparisons). However, no differences between groups based on mTBI history were found for total white matter volume or in any other cortical or subcortical structures examined. A subsequent moderation analysis found that CRF was predominantly non-influential on the association between mTBI history and the MRI-quantified measures of brain volume. While unexpected, the findings suggest that a history of mTBI can lead to grey matter alterations in the ageing brain. However, concurrent variations in the CRF level did not influence the differences in brain volume found based on mTBI exposure status.


Bioactive Suture with Added Innate Defense Functionality for the Reduction of Bacterial Infection and Inflammation.
Surgical site infections (SSI) are a clinical and economic burden. Suture-associated SSI may develop when bacteria colonize the suture surface and form biofilms that are resistant to antibiotics. Thrombin-derived C-terminal peptide (TCP)-25 is a host defense peptide with a unique dual mode of action that can target both bacteria and the excessive inflammation induced by bacterial products. The peptide demonstrates therapeutic potential in preclinical in vivo wound infection models. In this study, the authors set out to explore whether TCP-25 can provide a new bioactive innate immune feature to hydrophilic polyglactin sutures (Vicryl). Using a combination of biochemical, biophysical, antibacterial, biofilm, and anti-inflammatory assays in vitro, in silico molecular modeling studies, along with experimental infection and inflammation models in mice, a proof-of-concept that TCP-25 can provide Vicryl sutures with a previously undisclosed host defense capacity, that enables targeting of bacteria, biofilms, and the accompanying inflammatory response, is shown.


[Allergenic mites (Acariformes, Pyroglyphidae) in house dust].
Paper is the second part of the literature review on house dust mites (including 1985). It deals with the diagnosis of the dust mite allergy, the nature of the mite allergens, distribution and population density of the mites in various premises, seasonal population dynamics and population age structure of the dermatophagoid mites, life cycle and breeding of Dermatophagoides pteronyssinus and D. farinae on different food substrates. The methods of the house dust mite control are discussed. The original data on the house dust mite distribution in Moscow is shown. A comparative estimation of the results of mite antigens in the house dust discovering by the acarological and three immunological methods are given.


Jagged1 immobilization to an osteoconductive polymer activates the Notch signaling pathway and induces osteogenesis.
Treatment of nonunion fractures is a significant problem. Common therapeutics, including autologous bone grafts and bone morphogenetic proteins, show well-established limitations. Therefore, a need persists for the identification of novel clinical therapies to promote healing. The Notch signaling pathway regulates bone development. Clinically, loss-of-function mutations to the Notch ligand Jagged1 decrease bone mass and increase fracture risk. Jagged1 is also the most highly upregulated ligand during fracture repair, identifying it as a potential target to promote bone formation. Therefore, the objective of this study was to develop a clinically translatable construct comprised of Jagged1 and an osteoconductive scaffold, and characterize its activity in human mesenchymal stem cells (hMSC). We first evaluated the effects of Jagged1 directly immobilized to a novel poly(β-amino ester) relative to indirect coupling via antibody. Direct was more effective at activating hMSC Notch target gene expression and osteogenic activity. We then found that directly immobilized Jagged1 constructs induced osteoblast differentiation. This is the first study to demonstrate that Jagged1 delivery transiently activates Notch signaling and increases osteogenesis. A positive correlation was found between Jagged1-induced Notch and osteogenic expression. Collectively, these results indicate that Jagged1 coupled to an osteogenic biomaterial could promote bone tissue formation during fracture healing.


Deaths of heroin users in a general practice population.
Recent evidence suggests that heroin users in the UK are 16 times more likely to die than otherwise expected, although causes of death are varied. The present investigation examines deaths of heroin users at a large Scottish general practice over a four-year period prior to 1 July 1985. A mortality rate of 9.72 per 1000 heroin-user patients per year was observed, roughly half that previously reported, although this difference did not prove to be statistically significant. A higher proportion of the observed deaths were attributed to heroin, and fewer to the misuse of other drugs, and it is speculated that this may reflect the practice's policy of not prescribing opiates to heroin users. Factors associated with heroin-user deaths are examined and areas identified where general practitioners may help to avert some of these deaths.


May-Thurner syndrome: can it be diagnosed by a single MR venography study?
We aimed to evaluate the longitudinal stability of left common iliac vein (LCIV) compression by the right common iliac artery on magnetic resonance venography (MRV). This retrospective study included 214 patients diagnosed with May-Thurner syndrome by MRV. We identified a subset of patients who underwent contrast-enhanced cross-sectional imaging of the pelvis six months before or anytime after the MRV and did not undergo any interventional venous procedures between the two studies; 36 patients met these criteria. The degree of venous compression was calculated in both the index and comparison study. On the index MRV, the mean compression of the LCIV was 62%. However, on the comparison study in the same patients, the mean compression was 39%. The mean change in degree of compression between the two studies was 23% (P < 0.0001), ranging from a 12% increase to 69% decrease in degree of compression on the comparison study. The compressed LCIV on a single MRV study was not stable over time and thus may be insufficient to diagnose May-Thurner syndrome.


[Role of Mycoplasma infection in pediatric pathology].
The review presents data from the literature showing the variability of manifestations of mycoplasmal infection (M. pneumoniae, M. hominis, T-strain) in childhood. The etiological role of M. pneumoniae (as a monoantigen and in association with respiratory viruses) in acute respiratory infections and pneumonias has been established. M. pneumoniae also plays a certain role in the development of attacks of bronchial asthma and chronic recurrent pneumonias. M. hominis, being an urogenital mycoplasma, may also be the causative agent of acute respiratory infections and pneumonias. A high rate of infection of newborn babies with M. hominis and T-strains is noted. There is evidence indicating frequent and generalized mycoplasmal infection in infants in the perinatal period. In addition to changes in the lungs, mycoplasmal infection produces lesions in the heart, liver, kidneys, central nervous system and other organs, produces the development of hemolytic anemia and thrombocytopenia. Some studies indicate the possibility of intrauterine mycoplasmal infection and its terotogenic effect on the human fetus.


Anti-Inflammatory Activity of Exopolysaccharides from Phormidium sp. ETS05, the Most Abundant Cyanobacterium of the Therapeutic Euganean Thermal Muds, Using the Zebrafish Model.
The Euganean Thermal District (Italy) represents the oldest and largest thermal center in Europe, and its therapeutic mud is considered a unique product whose beneficial effects have been documented since Ancient Roman times. Mud properties depend on the heat and electrolytes of the thermal water, as well as on the bioactive molecules produced by its biotic component, mainly represented by cyanobacteria. The investigation of the healing effects of compounds produced by the Euganean cyanobacteria represents an important goal for scientific validation of Euganean mud therapies and for the discovering of new health beneficial biomolecules. In this work, we evaluated the therapeutic potential of exopolysaccharides (EPS) produced by Phormidium sp. ETS05, the most abundant cyanobacterium of the Euganean mud. Specifically, Phormidium EPS resulted in exerting anti-inflammatory and pro-resolution activities in chemical and injury-induced zebrafish inflammation models as demonstrated using specific transgenic zebrafish lines and morphometric and expression analyses. Moreover, in vivo and in vitro tests showed no toxicity at all for the EPS concentrations tested. The results suggest that these EPS, with their combined anti-inflammatory and pro-resolution activities, could be one of the most important therapeutic molecules present in the Euganean mud and confirm the potential of these treatments for chronic inflammatory disease recovery.


Over the Scope Clips for Treatment of Acute Nonvariceal Gastrointestinal Bleeding in Children Are Safe and Effective.
There is little published experience with the use of over-the-scope clips (OTSCs) in pediatric patients. The aim of this study is to present our single-center experience utilizing OTSCs for nonvariceal gastrointestinal (GI) bleeding. This is a retrospective case series of pediatric patients who underwent endoscopic management of GI bleeding during which OTSCs were used. Eleven cases of OTSC utilization for hemostasis were identified in 10 unique patients between November 2014 and May 2016. The median age at intervention was 14.7 years (range 3.9-16.8 years) and median weight was 39 kg (range 17.4-85.8 kg). Technical success and hemostasis were achieved in all cases and there were no complications. Median follow-up was 32.9 months (range 21.2-39.4 months). All nonanastomotic ulcers (4), polypectomy bleeding (2), and sphincterotomy bleeding (1) had no evidence of recurrent GI bleeding at last follow-up. Two patients with anastomotic ulcerations required additional medical interventions. Our series demonstrates the safety and effectiveness of the OTSCs in the pediatric population for acute GI bleeding throughout the GI tract. In our experience, it is effective for nonanastomotic ulcers, postpolypectomy bleeding, and postsphincterotomy bleeding even when other hemostatic techniques have failed. OTSCs may be less effective in the setting of anastomotic ulcerations, reaffirming the refractory nature of these lesions.


Systemic Par-4 inhibits non-autochthonous tumor growth.
The tumor suppressor protein Par-4 (Prostate apoptosis response-4) is spontaneously secreted by normal and cancer cells. Extracellular Par-4 induces caspase-dependent apoptosis in cancer cell cultures by binding, via its effector SAC domain, to cell surface GRP78 receptor. However, the functional significance of extracellular Par-4/SAC has not been validated in animal models. We show that Par-4/SAC-transgenic mice express systemic Par-4/SAC protein and are resistant to the growth of non-autochthonous tumors. Consistently, secretory Par-4/SAC pro-apoptotic activity can be transferred from these cancer-resistant transgenic mice to cancer-susceptible mice by bone marrow transplantation. Moreover, intravenous injection of recombinant Par-4 or SAC protein inhibits metastasis of cancer cells. Collectively, our findings indicate that extracellular Par-4/SAC is systemically functional in inhibition of tumor growth and metastasis progression, and may merit investigation as a therapy.


Synthesis of a carborane-substituted bis(phosphanido) cobaltate(i), ligand substitution, and unusual P4 fragmentation.
Oxidative addition of the P-P single bond of an ortho-carborane-derived 1,2-diphosphetane (1,2-C2(PMes)2B10H10) (Mes = 2,4,6-Me3C6H2) to cobalt(-i) and nickel(0) sources affords the first heteroleptic complexes of a carborane-bridged bis(phosphanido) ligand. The complexes also incorporate labile ligands suitable for further functionalisation. Thus, the cobalt(i) complex [K([18]crown-6)][Co{1,2-(PMes)2C2B10H10}(cod)] (cod = 1,5-cyclooctadiene) bearing a labile cyclooctadiene ligand undergoes facile ligand exchange reactions with isonitriles and tert-butyl phosphaalkyne with retention of the bis(phosphanido) ligand. However, in the reaction with one equivalent of P4, the electron-rich bis(phosphanido) moiety abstracts a single phosphorus atom with formation of a new P3 chain, while the remaining three P atoms derived from P4 form an η3-coordinating cyclo-P3 ligand. In contrast, when the same reaction is performed with two equivalents of the cobalt(i) complex, a dinuclear product is formed which features an unusual P4 chain in its molecular structure.


Modulatory effects of garlic, ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-nicotinamide diabetic rats.
Spices which show hypoglycaemic, hypolipidaemic and antioxidant activities may have a role in the treatment of diabetes and its complications. The present study aimed to compare the modulatory effects of garlic, ginger, turmeric and their mixture on the metabolic syndrome and oxidative stress in streptozotocin (STZ)-nicotinamide diabetic rats. Diabetes was induced in overnight fasted rats by a single intraperitoneal injection of STZ (65 mg/kg body weight) and nicotinamide (110 mg/kg body weight, 15 min before STZ injection). Diabetic rats orally received either distilled water (as vehicle) or 200 mg/kg body weight of garlic bulb, ginger rhizome or turmeric rhizome powder suspension separately or mixed together (GGT mixture) for twenty-eight consecutive days. The results showed that these spices and their mixture significantly alleviated (80-97 %, P < 0·05-0·001) signs of the metabolic syndrome (hyperglycaemia and dyslipidaemia), the elevation in atherogenic indices and cellular toxicity in STZ-nicotinamide diabetic rats by increasing the production of insulin (26-37 %), enhancing the antioxidant defence system (31-52 %, especially GSH) and decreasing lipid peroxidation (60-97 %). The greatest modulation was seen in diabetic rats that received garlic and the GGT mixture (10-23 % more than that in the ginger and turmeric groups). In conclusion, garlic or the mix including garlic appears to have an impact on each of the measures more effectively than ginger and turmeric and may have a role in alleviating the risks of the metabolic syndrome and cardiovascular complications.


In situ observations on the dentition and oral cavity of the Neanderthal skeleton from Altamura (Italy).
The Neanderthal specimen from Lamalunga Cave, near Altamura (Apulia, Italy), was discovered during a speleological survey in 1993. The specimen is one of the most complete fossil hominins in Europe and its state of preservation is exceptional, although it is stuck in calcareous concretions and the bones are mostly covered by calcite depositions. Nevertheless, it is possible to carry out some observations on craniodental features that have not previously been described. In this work, we present an account of the oral cavity, made possible by the use of a videoscope, which allowed us to reach some hidden parts of the mandible and palate. This is the first detailed overview of the teeth and maxillary bones of the Neanderthal skeleton from Altamura. The dentition is almost complete. However, two teeth (upper right P3 and upper left M1) were lost ante mortem and four teeth (lower right I1 and P3 and lower left I1 and I2) were lost most probably post mortem. Dental wear is marked. The erupted M3s and the inversion of the compensating curve of Wilson in the M1s and M2s but not in the M3s suggest that the individual is fully adult, but not old. Although most of the teeth have their roots exposed for several millimeters, the periodontal bone appears to be in good condition overall, except in correspondence of the two ante-mortem tooth losses. X-rays of the anterior teeth show a periapical lesion, probably linked to the advanced dental wear. We also observed a weak expression of taurodontism in the posterior dentition and the presence of a retromolar space, features consistent with an attribution to the Neanderthal hypodigm; this attribution is also supported by aspects of the cranial morphology, the morphometric analysis of the scapula and preliminary mtDNA data. There is also a well-developed palatine torus, to the best of our knowledge a feature not previously described in Neanderthals.


Zero-order noise suppression with various space-shifting manipulations of reconstructed images in digital holography.
In this paper, we describe various numerical space-shifting manipulations of the reconstructed images to remove the dc noise in the reconstruction, in terms of the periodicity characteristics of images in digital holography. The theoretical interpretation on different reconstruction periods of the image and the dc noise is described in detail for the first time, to the best of our knowledge. It is related to CCD sampling periods or frequencies for the fringes and the dc term of a hologram. With the calculations of Hadamard product of two different spatially shifted images and subsequent extraction of the root of it, the dc noise can be suppressed effectively and a clear image with the original intensity contrast can be obtained at the center in the hologram reconstruction, particularly when the image and the dc noise are completely or partially superposed with each other. The experiments for both in-line and off-axis imaging cases show that all results are completely consistent with theoretical predictions.


P53 in human melanoma fails to regulate target genes associated with apoptosis and the cell cycle and may contribute to proliferation.
Metastatic melanoma represents a major clinical problem. Its incidence continues to rise in western countries and there are currently no curative treatments. While mutation of the P53 tumour suppressor gene is a common feature of many types of cancer, mutational inactivation of P53 in melanoma is uncommon; however, its function often appears abnormal. In this study whole genome bead arrays were used to examine the transcript expression of P53 target genes in extracts from 82 melanoma metastases and 6 melanoma cell lines, to provide a global assessment of aberrant P53 function. The expression of these genes was also examined in extracts derived from diploid human melanocytes and fibroblasts. The results indicated that P53 target transcripts involved in apoptosis were under-expressed in melanoma metastases and melanoma cell lines, while those involved in the cell cycle were over-expressed in melanoma cell lines. There was little difference in the transcript expression of P53 target genes between cell lines with null/mutant P53 compared to those with wild-type P53, suggesting that altered expression in melanoma was not related to P53 status. Similarly, down-regulation of P53 by short-hairpin RNA (shRNA) had limited effect on P53 target gene expression in melanoma cells, whereas there were a large number of P53 target genes whose mRNA expression was significantly altered by P53 inhibition in melanocytes. Analysis of whole genome gene expression profiles indicated that the ability of P53 to regulate genes involved in the cell cycle was significantly reduced in melanoma cells. Moreover, inhibition of P53 in melanocytes induced changes in gene expression profiles that were characteristic of melanoma cells and resulted in increased proliferation. Conversely, knockdown of P53 in melanoma cells resulted in decreased proliferation. These results indicate that P53 target genes involved in apoptosis and cell cycle regulation are aberrantly expressed in melanoma and that this aberrant functional activity of P53 may contribute to the proliferation of melanoma.


Recent trends in stimulant medication use among U.S. children.
Stimulant medications, such as methylphenidate and amphetamines, are commonly prescribed to treat attention deficit hyperactivity disorder. Stimulant use increased fourfold from 1987 (0.6%) to 1996 (2.4%) among subjects 18-year-old and younger in the U.S. The aim of this study was to determine whether pediatric use of stimulants continued to rise during the period 1997-2002. The Medical Expenditure Panel Survey (MEPS) database for the years 1997-2001 was analyzed. The MEPS is a yearly survey of a nationally representative sample of civilian, noninstitutionalized U.S. households, conducted by the U.S. Agency for Health Care Research and Quality. Previously reported estimates from the 1996 MEPS and the 1987 National Medical Expenditure Survey, the predecessor to MEPS, were also replicated to compare recent trends to changes between 1987 and 1996. The prevalence use of stimulants among subjects under 19 years of age was 2.7% (95% C.I. 2.3-3.1) in 1997 and 2.9% (95% C.I. 2.5-3.3) in 2002, with no statistically significant change during these 6 years. Likewise, when pooling data across years and comparing the rate in 1997-1998 (2.8%) with the rate in 2001-2002 (3.0%), no statistically significant changes emerged. Use was highest among 6-12 year olds (4.8% in 2002), as compared with 3.2% among 13-19 year olds and 0.3% among children under 6. An estimated 2.2 million (95% C.I. 1.9-2.6) children received stimulant medication in 2002 as compared to 2.0 million (95% C.I. 1.7-2.3) in 1997. The steep increase in the utilization of stimulants among children 18 years and younger that occurred over the 1987-1996 period attenuated in the following years through 2002, and has remained stable among very young children.


Restricted protein phosphatase 2A targeting by Merkel cell polyomavirus small T antigen.
Merkel cell polyomavirus (MCV) is a newly discovered human cancer virus encoding a small T (sT) oncoprotein. We performed MCV sT FLAG-affinity purification followed by mass spectroscopy (MS) analysis, which identified several protein phosphatases (PP), including PP2A A and C subunits and PP4C, as potential cellular interacting proteins. PP2A targeting is critical for the transforming properties of nonhuman polyomaviruses, such as simian virus 40 (SV40), but is not required for MCV sT-induced rodent cell transformation. We compared similarities and differences in PP2A binding between MCV and SV40 sT. While SV40 sT coimmunopurified with subunits PP2A Aα and PP2A C, MCV sT coimmunopurified with PP2A Aα, PP2A Aβ, and PP2A C. Scanning alanine mutagenesis at 29 sites across the MCV sT protein revealed that PP2A-binding domains lie on the opposite molecular surface from a previously described large T stabilization domain (LSD) loop that binds E3 ligases, such as Fbw7. MCV sT-PP2A interactions can be functionally distinguished by mutagenesis from MCV sT LSD-dependent 4E-BP1 hyperphosphorylation and viral DNA replication enhancement. MCV sT has a restricted range for PP2A B subunit substitution, inhibiting only the assembly of B56α into the phosphatase holoenzyme. In contrast, SV40 sT inhibits the assembly of B55α, B56α and B56ε into PP2A. We conclude that MCV sT is required for Merkel cell carcinoma growth, but its in vitro transforming activity depends on LSD interactions rather than PP2A targeting. Merkel cell polyomavirus is a newly discovered human cancer virus that promotes cancer, in part, through expression of its small T (sT) oncoprotein. Animal polyomavirus sT oncoproteins have been found to cause experimental tumors by blocking the activities of a group of phosphatases called protein phosphatase 2A (PP2A). Our structural analysis reveals that MCV sT also displaces the B subunit of PP2A to inhibit PP2A activity. MCV sT, however, only displaces a restricted subset of PP2A B subunits, which is insufficient to cause tumor cell formation in vitro. MCV sT instead transforms tumor cells through another region called the large T stabilization domain. The PP2A targeting and transforming activities lie on opposite faces of the MCV sT molecule and can be genetically separated from each other.


Concordance between DSM-IV and DSM-5 criteria for delirium diagnosis in a pooled database of 768 prospectively evaluated patients using the delirium rating scale-revised-98.
The Diagnostic and Statistical Manual fifth edition (DSM-5) provides new criteria for delirium diagnosis. We examined delirium diagnosis using these new criteria compared with the Diagnostic and Statistical Manual fourth edition (DSM-IV) in a large dataset of patients assessed for delirium and related presentations. Patient data (n = 768) from six prospectively collected cohorts, clinically assessed using DSM-IV and the Delirium Rating Scale-Revised-98 (DRS-R98), were pooled. Post hoc application of DRS-R98 item scores were used to rate DSM-5 criteria. 'Strict' and 'relaxed' DSM-5 criteria to ascertain delirium were compared to rates determined by DSM-IV. Using DSM-IV by clinical assessment, delirium was found in 510/768 patients (66%). Strict DSM-5 criteria categorized 158 as delirious including 155 (30%) with DSM-IV delirium, whereas relaxed DSM-5 criteria identified 466 as delirious, including 455 (89%) diagnosed by DSM-IV (P <0.001). The concordance between the different diagnostic methods was: 53% (ĸ = 0.22) between DSM-IV and the strict DSM-5, 91% (ĸ = 0.82) between the DSM-IV and relaxed DSM-5 criteria and 60% (ĸ = 0.29) between the strict versus relaxed DSM-5 criteria. Only 155 cases were identified as delirium by all three approaches. The 55 (11%) patients with DSM-IV delirium who were not rated as delirious by relaxed criteria had lower mean DRS-R98 total scores than those rated as delirious (13.7 ± 3.9 versus 23.7 ± 6.0; P <0.001). Conversely, mean DRS-R98 score (21.1 ± 6.4) for the 70% not rated as delirious by strict DSM-5 criteria was consistent with suggested cutoff scores for full syndromal delirium. Only 11 cases met DSM-5 criteria that were not deemed to have DSM-IV delirium. The concordance between DSM-IV and the new DSM-5 delirium criteria varies considerably depending on the interpretation of criteria. Overly-strict adherence for some new text details in DSM-5 criteria would reduce the number of delirium cases diagnosed; however, a more 'relaxed' approach renders DSM-5 criteria comparable to DSM-IV with minimal impact on their actual application and is thus recommended.


Mechanisms of chemoresistance in cancer stem cells.
Chemotherapy is one of the standard methods of treatment in many cancers. While chemotherapy is often capable of inducing cell death in tumors and reducing the tumor bulk, many cancer patients experience recurrence and ultimately death because of treatment failure. In recent years, cancer stem cells (CSCs) have gained intense interest as key tumor-initiating cells that may also play an integral role in recurrence following chemotherapy. As such, a number of mechanisms of chemoresistance have been identified in CSCs. In this review, we describe a number of these mechanisms of chemoresistance including ABC transporter expression, aldehyde dehydrogenase (ALDH) activity, B-cell lymphoma-2 (BCL2) related chemoresistance, enhanced DNA damage response and activation of key signaling pathways. Furthermore, we evaluate studies that demonstrate potential methods for overcoming chemoresistance and treating chemoresistant cancers that are driven by CSCs. By understanding how tumor-initiating cells such as CSCs escape chemotherapy, more informed approaches to treating cancer will develop and may improve clinical outcomes for cancer patients.


Human-rodent contact and infection with lymphocytic choriomeningitis and Seoul viruses in an inner-city population.
We collected 1180 sera and 1363 questionnaires with information on demography, rodent exposure, and history of travel from persons visiting a sexually transmitted disease (STD) clinic in Baltimore between 1986-1988. Serological tests for two rodent-borne viruses detected antibodies to lymphocytic choriomeningitis virus (LCMV) in 54 individuals (4.7%; n = 1149) and antibodies to Seoul virus (SEOV) in three persons (0.25%; n = 1180). Antibody prevalence to LCMV increased with age, but there were no racial or sexual differences. Neutralization tests and questionnaire responses implicated a domestic, rat-borne hantavirus as the source of SEOV antibody. Self-reported human-rodent contact indicated more exposure to house mice than rats within residences, although rats were more commonly sighted on streets. Infections with rodent-borne viruses were rare compared to the high rates of reported contact.


Pharmacy support in developing prescribing skills.
Prescribing medicines is one of the most common interventions in health care, so even a small percentage of prescribing errors can affect many patients. Many of these errors are prevented by the intervention of pharmacists. Research has identified gaps in medical education and training that contribute to these errors. More effective learning opportunities for prescribing at undergraduate level will help to improve the preparation of junior doctors for their role. Traditionally, doctors have acquired their prescribing skills through an apprenticeship model. Given the complexity of current health care and increasing polypharmacy, a more systematic approach to safe prescribing is required. The pharmacist can have a key role in education and the practice of safe prescribing. Final-year students at the University of Dundee Medical School are invited to undertake sessions to rehearse safe prescribing practices using an objective structured clinical examination (OSCE) format. This helps to recreate the time pressures of practice with a focus on the elements of safe prescribing for patients. On a simulated ward, students rehearse six situations that represent the basis of commonly reported prescribing errors. Each scenario has four prescribing related tasks, one of which is feedback from a pharmacist. An evaluation of this approach and students' self-reported learning indicated that it was a useful way of enhancing awareness of errors and of increasing confidence. The pharmacist can have a key role in education and the practice of safe prescribing There are several benefits for students in having pharmacists design and facilitate the OSCE clinical scenarios, which include the immediate learning of accurate prescribing as well as the advisory role that the pharmacists play.


Traumatic Spinal Cord Injury Care in Canada: A Survey of Canadian Centers.
Specialized centers of care for persons sustaining a traumatic spinal cord injury (tSCI) have been established in many countries, but the ideal system of care has not been defined. The objective of this study was to describe care delivery, with a focus on structures and services, for persons with tSCI in Canada. A survey was sent to 26 facilities (12 acute, 11 rehabilitation, and three integrated) from eight provinces participating in the Access to Care and Timing project. The survey included questions about: 1) care provision; 2) structural attributes and; 3) service availability. Survey completion rate was 100%. Data sources used to complete the survey were the Rick Hansen Spinal Cord Injury Registry, other hospital databases, clinical protocols, and subject matter experts. Acute and rehabilitation care provided by integrated facilities were described separately, resulting in data from 15 acute and 14 rehabilitation facilities. The number of admissions for tSCI over a 12-month period between 2009-2011 ranged from 17 to 104 (median 39), and 11 to 96 (median 32), for acute and rehabilitation facilities, respectively. Grouping of patients was reported by 8/15 acute and 10/14 rehabilitation facilities. Criteria for admission to the inpatient rehabilitation facilities varied among facilities (25 different criteria reported). Results from the survey revealed similarities in the basic structure and the provision of general services, but also some differences in the degree of specialization of care for persons with tSCI. Continued work on the impact of specialized care for both the patient and healthcare system is needed.